The Growing Relevance of Immunoregulation in Pediatric Brain Tumors

SIMPLE SUMMARY: Pediatric brain tumors are the leading cause of childhood cancer-related deaths worldwide. Considering the dismal prognosis and the adverse effects of chemo- and radio-therapy, strategies targeting the tumor microenvironment represent a promising approach for improving the efficacy of standard and targeted molecular therapeutics. This review presents the current understanding of the juvenile innate immune system in the central nervous system and gives insights into the brain as a unique tumor site. Moreover, we outline an explorative overview of studies about the tumor microenvironment of pediatric brain tumors and its role in tumor progression and therapy resistance. We further put attention to the potential immunomodulatory effects of current therapeutic regimens. Finally, we provide a perspective regarding the present immunotherapeutic treatment options and future clinical implications of targeting the immune cells. ABSTRACT: Pediatric brain tumors are genetically heterogeneous solid neoplasms. With a prevailing poor prognosis and widespread resistance to conventional multimodal therapy, these aggressive tumors are the leading cause of childhood cancer-related deaths worldwide. Advancement in molecular research revealed their unique genetic and epigenetic characteristics and paved the way for more defined prognostication and targeted therapeutic approaches. Furthermore, uncovering the intratumoral metrics on a single-cell level placed non-malignant cell populations such as innate immune cells into the context of tumor manifestation and progression. Targeting immune cells in pediatric brain tumors entails unique challenges but promising opportunities to improve outcome. Herein, we outline the current understanding of the role of the immune regulation in pediatric brain tumors.